Juvenile Macular Degeneration (JMD) or so-called Idiopathic Subretinal Neovascularization is a major cause of macula-related blindness in people less than 50 years old. These patients develop subretinal neovascularization and disciform scarring of the macula which resembles senile macular degeneration, or more accurately, the Presumed Ocular Histoplasmosis Syndrome (POHS). However, the clinical features of this disease, notably the lack of drusen and the absence of systemic manifestations of histoplasmosis, distinguish this macular disorder from its counterpart in the elderly eye and in the patient from a geographic area which is endemic to histoplasmosis. In areas of the U.S. where histoplasmosis is prevalent, JMD patients are presumed to have ocular histoplasmosis, accounting for their macular manifestations. In the greater New York-New Jersey area, histoplasmosis is not endemic, with histoplasmin skin sensitivity studies indicating that only 0-2% of patients tested are positive to this antigen. Although the clinical ocular features of JMD resemble those seen in POHS, the pathogensis of JMD is obviously related to other etiologic factors. This study will investigate the natural course of JMD and the environmental factors that may relate to disease development. Nearly 100 patients have been studied and followed by Dr. Lawrence Yannuzzi. The salient clinical features of the disease will be described, including particular predispositions in certain races, sex and other factors. Possible questions such as the incidence of bilaterality and the visual course of the involved and non-involved eyes will be studied. An extensive epidemiological survey has been prepared, investigating a wide range of host and environmental factors. Planned laboratory studies will include HLA titers, specific skin testing and serological analyses for other conditions associated with subretinal neovascularization. A further assessment of immunocompetence will be done in collaboration with Sloan-Kettering Institute. This testing will include lymphocyte transformation to compare the immune response of JMD patients and controls to histoplasmin and other antigens in vitro.